Alterations of the adhesive interaction between cells and components of the interstitial matrix such as collagen are doubtlessly important in the invasive and metastatic behavior of malignant cells. Excepting the rapidly growing body of knowledge concerning fibronectin, little information exists on the molecular bases of cell-matrix interaction. Clearly, surface macromolecules other than fibronectin are involved in adhesion, as are components of the cytoskeleton, but biochemical details of these involvements are scantly. Moreover, the effects of clear cut alterations of in vitro adhesiveness on the invasive or metastatic behavior cells in situ or in vivo are unknown. The present proposal intends to explore the molecular basis and biological consequences of altered cell-substratum adhesiveness using membrane biochemistry and somatic cell genetics as tools. We have isolated and partially characterized a series of variant clones of CHO cells which are defective in their ability to adhere to a collagen substratum; we suspect that the defect may be due to an altered surface binding of fibronectin. We intend to investigate the molecular aspects of adhesion by comparing the membrane biochemistry of the variant clones with that of wild type CHO clones. We will examine the surface glycoproteins, glycosaminoglycans and glycolipids of the membranes of both types of cells. We will also examine the role of cytoskeletal sol-gel transitions in the adhesion of both wild type and variant cells. In addition we will study the biological behavior of wild type and adhesion variant CHO cells in terms of invasiveness in the chick chorioallantoic membrane and metastasis formation in nude mice.